We shall study the interaction of mouse T-helper cells, T-suppressor cells, B cells, and macrophages in the immune response to two proteins, lysozyme and beta-galactosidase. Our overall objective is to ascertain whether there are differences among these cell types in epitope recognition. Earlier evidence has shown us that key suppressive determinants exist on these two proteins. We will study how the presentation of antigen by macrophages influences the T-cell recognition, what specificities are characteristic of T-helper and T-suppressor subpopulations and how this compares with B cell populations, and how the nature of the immune response is altered by separating suppressor from helper determinants, or by fracturing or covering suppressive determinants. We will study the effect of anti-idiotypic antibodies raised against B-cell hybridomas and T cell hybridomas of defined specificity (anti-lysozyme and anti-beta galactosidase) in shifting the regulatory balance. We would like to clarify the crossover between idiotypic and antigenic regulatory universes. The cellular target of suppressor cells will be defined. The major assay system to be employed are in vitro T-dependent antibody forming systems where our protein antigens act as carriers for anti-hapten responses, and antigen-dependent T-proliferation systems using primed lymph nodes and peritoneal-exudate T cells.